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A biodegradable micellar drug delivery system with a pH-responsive sheddable PEG shell was developed using an acetal-linked poly(ethylene glycol)-block-polylactide (PEG-a-PLA) copolymer and applied to the tumoral release of paclitaxel (PTX). The micelles with a diameter of ∼100 nm were stable in PBS at pH 7.4, started shedding the shell and aggregating slowly at pH 6.5, and decomposed faster at pH 5.5. PTX-loaded micelles (M-PTX) with a drug loading of 6.9 wt % exhibited pH-triggered PTX release in simulated tumoral acidic environments corresponding to the extracellular and intracellular spaces. In vitro experiments showed that the micelles were noncytotoxic to different cell lines, while M-PTX inhibited the proliferation and promoted the apoptosis of Hela cells. An in vivo study with Hela tumor-bearing mice indicated that M-PTX efficiently inhibited tumor growth. Because of these properties, the PEG-a-PLA micellar system appears to have bright prospects as a tumor-targeting drug carrier.

pH-Responsive Poly(Ethylene Glycol)-block-Polylactide Micelles for Tumor-Targeted Drug Delivery